Lessons Learned From the Implementation of a Pilot Study on Self-collected Specimen Return by Sexual Minority Men (Project Caboodle!): Qualitative Exploration

Background Self-collection of specimens at home and their return by mail might help reduce some of the barriers to HIV and bacterial sexually transmitted infection (STI) screening encountered by gay, bisexual, and other men who have sex with men (GBMSM). To evaluate the benefits and challenges of bringing this approach to scale, researchers are increasingly requesting GBMSM to return self-collected specimens as part of web-based sexual health studies. Testing self-collected hair samples for preexposure prophylaxis drug levels may also be a viable option to identify GBMSM who face adherence difficulties and offer them support. Objective Project Caboodle! sought to evaluate the acceptability and feasibility of self-collecting at home and returning by mail 5 specimens (a finger-stick blood sample, a pharyngeal swab, a rectal swab, a urine specimen, and a hair sample) among 100 sexually active GBMSM in the United States aged between 18 and 34 years. In this manuscript, we aimed to describe the key lessons learned from our study’s implementation and to present recommendations offered by participants to maximize the rates of self-collected specimen return. Methods Following the specimen self-collection phase, a subset of 25 participants (11 who returned all 5 specimens, 4 who returned between 1 and 4 specimens, and 10 who did not return any specimens) was selected for in-depth interviews conducted via a videoconferencing platform. During the session, a semistructured interview guide was used to discuss the factors influencing decisions regarding returning self-collected specimens for laboratory processing. The transcripts were analyzed using template analysis. Results University branding of web-based and physical materials instilled a sense of trust in participants and increased their confidence in the test results. Shipping the specimen self-collection box in plain unmarked packaging promoted discretion during transit and on its receipt. Using different colored bags with matching color-coded instructions to self-collect each type of specimen minimized the potential for confusion. Participants recommended including prerecorded instructional videos to supplement the written instructions, providing information on the importance of triple-site bacterial STI testing, and adding a reminder of the types of testing that would and would not be conducted on hair samples. Participants also suggested tailoring the specimen self-collection box to include only the tests that they might be interested in completing at that time, adding real-time videoconferencing to the beginning of the study to introduce the research team, and sending personalized reminders following the delivery of the specimen self-collection box. Conclusions Our results offer valuable insights into aspects that facilitated participant engagement in self-collected specimen return, as well as areas for potential improvement to maximize return rates. Our findings can help guide the design of future large-scale studies and public health programs for home-based HIV, bacterial STI, and preexposure prophylaxis adherence testing. International Registered Report Identifier (IRRID) RR2-10.2196/13647


Introduction
Background Gay, bisexual, and other men who have sex with men (GBMSM) in the United States are heavily affected by HIV and bacterial sexually transmitted infections (STIs) [1,2]. Sexual network characteristics and behavioral or biological factors (eg, multiple partners, condomless sex, and substance use) are known to increase susceptibility [3][4][5][6]. Timely detection and treatment are essential to reducing the burden of these infectious diseases among GBMSM. National recommendations state that all sexually active GBMSM should be screened for HIV, gonorrhea, and chlamydia at least annually and more frequently if warranted (eg, biannually or quarterly) depending on individual risk profiles [7,8]. Triple-site testing for gonorrhea and chlamydia, that is, testing at the pharyngeal, rectal, and urethral sites, is a crucial component of surveillance because STIs in the throat and rectum are often asymptomatic [9][10][11] and can be missed if urine-only screening is performed [12,13]. Despite concerted efforts by public health agencies at the national, state, and local levels, the annual rates of testing for HIV and bacterial STIs among GBMSM remain suboptimal [14,15].
Individual factors (eg, fear of a positive test result and low-risk perception), structural factors (eg, lack of transportation and limited access to culturally competent health care), socioeconomic factors (eg, stigma, discrimination, and inadequate health insurance coverage), and privacy factors (eg, concerns about being seen by friends or family members at a testing location) are well-documented barriers to HIV and bacterial STI screening among GBMSM [16][17][18]. Stay-at-home mandates during the early stages of the COVID-19 pandemic posed obstacles to seeking in-person services and resulted in substantially decreased rates of HIV and bacterial STI testing [19], a trend that persisted even after the relaxation of mandates [20]. As nonemergent health care operations return to full capacity, the importance of supplemental approaches to identify new infections among GBMSM and link them to medical care remains high. Self-collection of specimens at home for rapid testing or their return by mail for laboratory processing may help reduce some impediments to HIV and bacterial STI screening [21][22][23]. Self-collected finger-stick blood samples [24], pharyngeal swabs [25], rectal swabs [26], and urine specimens [27] have been found to be equally valid and reliable as clinician-collected samples for HIV and bacterial STI screening. To evaluate the benefits and challenges of bringing this approach to scale, researchers are increasingly requesting GBMSM to return self-collected specimens as part of web-based sexual health studies [28][29][30][31][32].
Since the 2012 approval of oral preexposure prophylaxis (PrEP) for HIV in the United States, the awareness and use of this prevention tool has steadily increased among GBMSM [33]. PrEP efficacy is highly dependent on adherence to the prescribed regimen [34][35][36] but taking a daily pill can be onerous for some individuals. Multiple studies conducted among GBMSM have found blood PrEP drug levels corresponding to <4 doses per week after 6 months of PrEP initiation [37][38][39][40]. Forgetting to take the medication every day, experiencing side effects (eg, headache and nausea), and missing follow-up appointments have been identified as common reasons for poor adherence [41,42]. In addition to blood tests, some objective measures of PrEP adherence used in previous research include pill counts, pharmacy refills, and electronic adherence monitors [43,44].
One specimen that has recently demonstrated utility in PrEP drug-level testing is hair [45][46][47][48][49]. Segmental analysis of hair samples can allow for an objective assessment of PrEP adherence over different time intervals [50,51]. Given that hair is a nonbiohazardous, easy-to-ship specimen that remains stable at ambient temperature, its self-collection and return for PrEP drug-level testing may be a viable option to identify GBMSM who face adherence difficulties and offer them support.

Objectives
Project Caboodle! sought to evaluate the acceptability and feasibility of self-collecting at home and returning by mail 5 specimens for HIV, bacterial STI, and potential PrEP drug-level testing among 100 sexually active GBMSM in the United States aged between 18 and 34 years. Complete details pertaining to the study protocol [52] and a description of the study results [53] have been published elsewhere. Participant-related activities were completed between March 2019 and April 2020. In this manuscript, we aimed to describe the key lessons learned from our study's implementation and to present recommendations offered by participants to maximize the rates of self-collected specimen return based on in-depth interviews with those who chose to return all, some, or none of the specimens.

Participant Recruitment
Participants were recruited via social media advertising on Facebook and Grindr. Individuals who clicked on the advertisements were directed to the study's landing page that included a brief overview of the protocol and a link to the informed consent form. Those who consented were asked to complete an eligibility screener. The eligibility criteria included being assigned male sex at birth, reporting a male gender identity, being 18 to 34 years of age, residing in the United States or dependent areas, not known to be living with HIV, having ≥2 male sex partners in the past 3 months, and expressing willingness to receive a specimen self-collection box at home. Those who were eligible were asked to provide their contact information (name, email address, mobile phone number, and preferred mailing address). Those who did not provide informed consent, did not meet the eligibility criteria, or did not provide verifiable contact information were directed to the Centers for Disease Control and Prevention website containing information and resources on HIV and bacterial STIs.

Study Procedures
In the first phase, 100 participants who completed a web-based survey were shipped a box containing instructions and materials to self-collect and return any of the following: a finger-stick blood sample (for HIV testing), a pharyngeal swab, a rectal swab, a urine specimen (for triple-site gonorrhea and chlamydia testing), and a hair sample (to assess its adequacy for potential PrEP drug-level testing). Participants were given a period of 6 weeks from receiving the box to returning self-collected specimens of their choice for laboratory processing by using envelopes affixed with prepaid FedEx shipping labels. No incentive, monetary or otherwise, was provided for completing this step. Test results were delivered back to participants by a counselor via a phone call or an email containing a link to a secure Box folder created specifically for each participant.
In the second phase, a subset of 25% (25/100) of participants (those who returned all 5 specimens: 11/39, 28%; those who returned between 1 and 4 specimens: 4 /12, 33%; and those who did not return any specimens: 10/49, 20%) was selected for in-depth interviews conducted via BlueJeans (Verizon Communications), a videoconferencing platform that allows compliance with the Health Insurance Portability and Accountability Act. Purposive sampling was used to ensure variations in age, race, and ethnicity. During the session, a semistructured interview guide was used to discuss the participants' decision-making regarding returning self-collected specimens for laboratory processing. Depending on the number and type of specimens returned by participants, the interviews were tailored to focus on factors that shaped their engagement or lack thereof.

Qualitative Analysis
The in-depth interviews were transcribed using Scribie, checked for accuracy against the original audio files, and uploaded to Dedoose (Socio Cultural Research Consultants), a web-based platform for collaborative qualitative data analysis. Transcripts were analyzed using template analysis, a style of thematic analysis that involves developing an initial coding template using a subset of the data, applying it to further data, and refining it using an iterative process [54]. In this method, it is permissible to start with some a priori themes that are likely to be relevant to the analysis. First, an initial coding template that included a mix of themes identified in advance (eg, characteristics of the specimen self-collection box and additional information desired during the study) and themes identified from 3 interviews (one each from participants who returned all, some, and none of the specimens) was developed. Next, this template was applied to more transcripts, discussed among the research team, and iteratively revised based on the identification of newly emergent themes. Six overarching themes were coded: (1) influence of university branding on study credibility, (2) matters related to the transit and receipt of the specimen self-collection box, (3) internal attributes of the specimen self-collection box, (4) desire for instructional videos and additional test-related information, (5) preference-based tailoring of the specimen self-collection box, and (6) experiences with communications from the research team. Each theme also had subthemes that emerged from the participants' narratives.

Ethics Approval
The study protocol was reviewed and approved by the Institutional Review Board of the University of Michigan in Ann Arbor (HUM00153673). Electronic informed consent was obtained from all individual participants included in the study. Verbal consent for audio recording and transcription was also obtained from all individual participants at the beginning of each in-depth interview. Participants received US $40 for completing a web-based survey in the first phase of the study and US $40 for completing an in-depth interview in the second phase of the study.

Sample Characteristics
The age of the participants of in-depth interviews ranged from 20 to 32 years, with the mean and median being 26 (SD 3.49) years. The sample of 25 participants was diverse with respect to race and ethnicity: 5 (20%) participants identified as non-Hispanic White; 4 (16%) as non-Hispanic Black; 7 (28%) identified as Asian; and 9 (36%) identified as Hispanic (irrespective of their race). Most participants had a college degree or a higher educational level (18/25, 72%), identified as gay (21/25, 84%), and were single (22/25, 88%). Regarding their recent sex behaviors, 40% (10/25) of participants engaged in condomless anal sex, and 76% (19/25) of participants engaged in condomless oral sex with ≥2 men in the past 3 months. Most participants (24/25, 96%) reported testing for HIV and two-thirds (17/25, 68%) reported testing for bacterial STIs in the past year. Finally, 44% (11/25) of participants indicated that they were using PrEP at the time of the study. This manuscript includes 30 verbatim excerpts from 18 participants (1-3 excerpts per participant).

Influence of University Branding on Study Credibility
University branding was used throughout the study, including the social media advertisements, the web-based survey, and the specimen self-collection box. Our use of the well-recognized University of Michigan Block "M" logo instilled a sense of trust in the participants whose sentiments are evident in the following excerpts:

Matters Related to the Transit and Receipt of the Specimen Self-collection Box
During the design phase, our research team recognized the importance of discretion while shipping the specimen self-collection box to prevent the inadvertent disclosure of the recipient's involvement in a study on sexual health for GBMSM. Receiving a plain unmarked package with no reference to the nature of the contents was appreciated by several participants:

Internal Attributes of the Specimen Self-collection Box
Several participants mentioned that upon opening the specimen self-collection box, they found its contents to be neatly organized:

Desire for Instructional Videos and Additional Test-Related Information
When asked how our specimen self-collection instructions could be enhanced, some participants recommended the inclusion of prerecorded instructional videos in addition to written instructions, especially for the finger-stick blood sample: Several participants did not remember why they were being asked to provide a hair sample by the time they received the specimen self-collection box, suggesting that the inclusion of a reminder on the types of testing that would and would not be performed on hair samples might be helpful:

Preference-Based Tailoring of the Specimen Self-collection Box
One theme that emerged from the participants' narratives was their desire for a customized specimen self-collection box that only included instructions and materials for those tests that they were interested in completing at that time: In addition to enhancing the overall experience, a potential benefit of tailoring the specimen self-collection box could be an improved rate of specimen return. Some participants described how they felt overwhelmed at the thought of self-collecting 5 specimens, which prevented them from proceeding any further:

Experiences With Communications From the Research Team
During discussions regarding their experiences with receiving communications from the research team at different time points, participants offered suggestions on types of further support that could help improve study engagement.
One participant recommended the addition of real-time videoconferencing at the beginning of the study to introduce the research team (instead of potentially including a prerecorded welcome video), as that would allow new participants to ask questions or discuss concerns:

Principal Findings
Several aspects of the implementation of Project Caboodle! were appreciated by the participants, as evidenced by their positive feedback during the in-depth interviews. Using the University of Michigan Block "M" logo in all study materials enhanced credibility; shipping the specimen self-collection box in plain unmarked packaging promoted discretion; and using different colored bags with matching color-coded instructions to self-collect each type of specimen minimized the potential for confusion. Participants also offered some constructive commentary, providing important lessons for future refinements to our processes that could help improve the rates of self-collected specimen return in subsequent work with GBMSM. They recommended including prerecorded instructional videos to supplement the written instructions, providing information on the importance of triple-site bacterial STI testing, and adding a reminder of the types of testing that would and would not be conducted on hair samples. They also suggested tailoring the specimen self-collection box based on individual preferences, adding real-time videoconferencing at the beginning of the study to introduce the research team, and sending personalized reminders following the delivery of the specimen self-collection box as practical strategies to bolster the likelihood of specimen return.
One feature of our study that contributed to its success was our consistent use of university branding on the social media advertisements, the web-based survey, and the specimen self-collection box. University academic logos are unique visual representations that signal institutional identity and can instill a sense of trust [55] and perceived competence [56] in the general public. Participants clearly valued the information regarding who was behind the research from the time point of their initial contact with one of our study's advertisements on Facebook or Grindr all the way through to their return of self-collected specimens to university-based laboratories and the receipt of test results. We were successful in recruiting a racially and ethnically diverse sample of 100 GBMSM from across the United States via social media advertising, and the proportion of specimens returned for laboratory processing in our study (51/100, 51%) was higher than that in 6 other studies (30%) recently completed with GBMSM that did not incentivize specimen return either [57]. Including university or institutional branding at different stages of participant interaction is an effective way to enhance a study's credibility and may facilitate the recruitment and retention of participants in future web-based HIV and bacterial STI prevention research.
The participants in our study also appreciated receiving the specimen self-collection box at their residence in plain unmarked packaging. This afforded privacy and prevented an inadvertent disclosure of their involvement in sexual health research to the mail carrier or to someone they lived with such as a roommate or parent. Given the stigma associated with HIV and bacterial STI testing [58,59], as well as PrEP use [60,61] among GBMSM, the use of discreet packaging reduces the potential for discomfort or harm if the contents of the package are revealed to someone other than the participant. For extra discretion, neither our primary package (ie, the specimen self-collection box containing instructions and materials) nor our secondary package (ie, the cardboard United Parcel Service box used for shipping the specimen self-collection box) made any reference to the nature of the contents. Studies with multiple self-collection points would particularly benefit from applying discretion while shipping packages to maintain participant's confidentiality and possibly reduce attrition. It might also help to offer participants the option of providing an alternative shipping address, such as a Post Office box or self-service parcel locker in case they have concerns about receiving a shipment at their residential address. Internal attributes of the specimen self-collection box that were well received by participants included its neat organization and our use of different colored bags with matching color-coded instructions for different types of specimens: red for a finger-stick blood sample, blue for a pharyngeal swab, green for a rectal swab, yellow for a urine specimen, and black for a hair sample. Of note, the bags and instructions were purposefully color-coded to align with the Project Caboodle! study logo [52]. Color coding is an effective strategy to enable recipients to easily distinguish between separate components included in a package [62,63] and could help reduce ambiguity during the process of self-collecting different types of specimens. Our research team strove for a minimalistic package design while ensuring the harmoniousness of various components inside the specimen self-collection box [64]. It is important that the contents of the package be well organized and easy to navigate independently, particularly in large-scale studies or public health programs in which there might be minimal interaction between the researchers or practitioners and participants or clients, respectively.
Shifting focus to avenues for improvement, some participants recommended the inclusion of prerecorded instructional videos in addition to written instructions, especially for the finger-stick blood sample, to allay their anxiety (by demonstrating how finger-stick blood self-collection differs from phlebotomy conducted in a clinic) and bolster their self-efficacy (by offering an opportunity to perform self-collection alongside someone in the video). We acknowledge that providing access to prerecorded instructional videos is becoming increasingly common in specimen self-collection research [65][66][67] and concur with those who emphasize that supplemental instructional resources should be accurate and easy to comprehend (including their availability in multiple languages) and should provide clear guidance on how to handle specimens after self-collection [23,68]. On the basis of participants' feedback, it might also be beneficial to highlight the importance of triple-site bacterial STI testing and reiterate the types of testing that would and would not be performed on hair samples. Extragenital gonococcal and chlamydial infections are prevalent among GBMSM [9][10][11] and may remain undiagnosed if urine-only screening is performed [12,13]. Educating sexually active GBMSM about the importance of triple-site bacterial STI testing might help improve return rates of pharyngeal swabs, rectal swabs, and urine specimens in subsequent studies. Similarly, reminding participants that returned hair samples would only be used for PrEP drug-level testing (and not for substance use or DNA testing) could alleviate possible skepticism and resistance to returning this specimen.
Another recommendation put forth by participants was potentially customizing the specimen self-collection box to include only instructions and materials for those tests that they were interested in completing at that time. The prospect of self-collecting 5 specimens was reported to be overwhelming by some participants, and it negatively influenced the likelihood of return despite having a choice to return only those specimens that they felt comfortable returning. Similar results were noted in another recent study with young GBMSM who were offered the option to self-collect and return a finger-stick blood sample for syphilis testing along with pharyngeal, urethral, and rectal swabs for gonorrhea and chlamydia testing [66]. Despite intending to return specimens, a subset of participants kept postponing self-collection, as they were overwhelmed by the process. Some participants in our study were also apprehensive about pricking their own finger. Those who were using PrEP were less inclined to return a finger-stick blood sample for HIV testing because of their established routine of testing at a clinic every 3 months while refilling their prescription. Contacting participants before shipping them a specimen self-collection box to inquire regarding which tests they desired to be performed might help improve return rates and reduce wastage of material, financial, and personnel resources.
Participants in our study also offered recommendations on the addition of communication strategies that could help improve engagement at multiple time points. Connecting with the research team via real-time videoconferencing at the beginning of the study would provide new participants with an opportunity to have their questions or concerns addressed and set the foundation for developing a rapport. Longitudinal studies with GBMSM should consider incorporating onboarding sessions conducted via real-time video conferencing if resources permit. Participants who did not return any specimens mentioned that receiving personalized reminders via their preferred modes of communication (eg, texts and emails) following the receipt of the specimen self-collection box might have prompted them to return the specimens. The reason we did not include reminders (or incentives) was to avoid influencing return rates in our acceptability and feasibility study. However, reminders have been shown to influence behaviors across a spectrum of health care issues and can help promote study engagement [69,70]. Returning test results via multiple communication channels is also a good practice as a phone call or real-time videoconferencing allows for the immediate provision of support and resources (especially in the case of a positive result) and a text or email allows for access to a copy of the results in the future.

Study Limitations
Caution should be exercised in generalizing our findings because our recruitment was restricted to GBMSM who were aged between 18 and 34 years and had accounts on Facebook or Grindr. Their opinions on factors shaping study engagement or lack thereof may differ from users of other social media or dating platforms and from those who do not have a presence on the web. In addition, only 3% (3/100) of the participants in our study resided in areas designated as rural by the Federal Office of Rural Health Policy, and none of them were interviewed. This limitation precludes our understanding of issues unique to rural residents (eg, difficulty returning specimens by mail in case they have to travel long distances to a shipping facility and paying a surcharge for package pickup if they live in an area deemed to be less accessible by shipping carriers). Our interviews were conducted only in English, which could have posed a language barrier for some participants. Finally, most interviews were completed before the COVID-19-related stay-at-home mandates came into effect, and it is possible that additional themes and subthemes may have emerged had we interacted with the participants during the pandemic.

Conclusions
Soliciting self-collected specimens for HIV, triple-site gonorrhea, and chlamydia, and PrEP drug-level testing from GBMSM might hold promise as a remote monitoring strategy for individuals at elevated risk. In-depth interviews with a subset of participants who returned all, some, or none of the specimens in our exploratory study offered valuable insights into aspects that facilitated their engagement as well as areas for potential improvement. Our results have pragmatic implications for the design of subsequent large-scale studies and public health programs for home-based HIV, bacterial STI, and PrEP adherence testing. This comprehensive overview of the key lessons learned from our study's implementation and recommendations offered by participants could help maximize the rates of self-collected specimen return in future web-based HIV and bacterial STI prevention research and practice.